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    Home > Tian Ruijun, Department of chemistry, South University of science and technology, published research results in the Journal of the National Academy of Sciences: helping the clinical use of targeted anticancer drugs

    Tian Ruijun, Department of chemistry, South University of science and technology, published research results in the Journal of the National Academy of Sciences: helping the clinical use of targeted anticancer drugs

    • Last Update: 2018-10-12
    • Source: Internet
    • Author: User
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    Recently, the project led by Tian Ruijun, associate professor of the Department of chemistry, South University of science and technology, and participated in by Li Pengfei, assistant professor of the Department of chemistry and Sun Ying, assistant professor of the Department of biology, has made progress in the field of chemical proteomics research The related achievements have been published in proceedings of the National Academy of Sciences National Academy of Sciences, PNAs), the title of the paper is "photoaffinity engineered protein scaffold for systematic exploration of native photosynthesine signaling complexes in more samples" (DOI: 10.1073 / PNAS 1805633115) This research work was mainly completed by Chu Bizhu, a postdoctoral researcher of Tian Ruijun's research group, and he an, a research assistant (co first author) The Department of chemistry of South University of science and technology is the first research unit, and Tian Ruijun, Li Pengfei and Sun Ying are co correspondents According to Tian Ruijun, Li Pengfei and Sun Ying (source: South University of science and Technology), protein is the most important substance in human body In addition to being the cornerstone of building life, there are more than 100000 kinds of interactions among proteins in human cells at any time These massive interactions assemble proteins into a variety of protein complexes with different functions, which perform and regulate almost all life processes and functions Through the precise regulation of post-translational modification of more than 200 proteins, protein complexes have the characteristics of dynamic changes in space-time For example, the phosphorylation of tyrosine with very low abundance is recognized and assembled by the Src homology 2 (SH2) domain, and is precisely and dynamically regulated by tyrosine kinase and phosphatase It is an important molecular regulatory mechanism for cancer and other major diseases Many anticancer drugs, such as gleevac, target on these proteins Proteomics research on tyrosine phosphorylated protein complexes has been a research hotspot in the field of basic biology However, due to the technical problems such as weak binding force between proteins and the presence of insoluble cell membrane, it is difficult to realize the in vivo system characterization of tumor and other clinical samples Chemical proteomics is a new subject which combines chemical biological technology and proteomic analysis technology organically It can realize in vivo and in vivo labeling and large-scale analysis of important drug targets and biomarkers This study developed a chemical proteomics technique to overcome the above challenges, and named it photo pTyr scaffold By introducing photoreaction group and enrichment group into SH2 domain with chemical probe containing three functional groups, covalent bond coupling and affinity enrichment of protein complex can be realized, which significantly improves the enrichment and identification ability of tyrosine phosphorylated protein complex with dynamic and weak interaction characteristics of human or animal tissue samples Using the chemical proteomics technology, the team successfully achieved high selective enrichment and large-scale proteomics analysis of tyrosine phosphorylated proteins and their complexes in human breast cancer samples Compared with the traditional immunohistochemistry technology, this technology improves the detection sensitivity of HER2, an important drug target protein, by about 100 times, which is expected to guide the clinical use of Herceptin more accurately What's more, this technology has found a potential new drug target PDGFRb for breast cancer patients with HER2 negative expression The experimental results of animal model of breast cancer show that the inhibition of the drug target can significantly inhibit the growth of breast cancer In a word, the research strategy of chemical proteomics is expected to provide help for the large-scale discovery of new generation cancer drug target proteins and biomarkers The project was supported by funds from the special subproject of protein machine of national key R & D plan, general project of National Natural Science Foundation, Guangdong Natural Science Foundation team project and discipline layout project of Shenzhen Science and technology innovation Commission; Shenzhen People's hospital provided relevant clinical samples and analysis for the research.
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